Naslov
N-glycan structures associated with activation of the complement system are increased in children with type 1 diabetes

Autori
Selak, Najda ; Kifer, Domagoj ; Simunović, Vesna ; Kaur, Simranjeet ; Cvetko, Ana ; Keser, Toma ; Pavić, Tamara ; Klarić, Lucija ; Pociot, Flemming ; Morahan, Grant ; Gornik, Olga

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
2nd GlycoCom 2018 and 1st Human Glycome Project Meeting book of abstract / - , 2018, 110-111

Skup
2nd GlycoCom 2018 and 1st Human Glycome Project Meeting

Mjesto i datum
Dubrovnik, Hrvatska, 03.10.2018. - 06.10.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Recenziran

Ključne riječi
type 1 diabetes ; N-glycosyation ; plasma proteins ; IgG ; complement

Sažetak
Type 1 diabetes (T1D) is a chronic disease characterized by the autoimmune destruction of pancreatic insulin-producing beta cells with the unknown cause. Alterations in glycosylation have been linked with various diseases and are emerging as potential biomarkers of a disease development or progress. In order to search for glycomic changes in T1D that could be associated with the disease onset, plasma samples of 1105 children and adolescents (0-18 years) diagnosed with T1D were collected within three months of diagnosis through the Danish Registry of Childhood and Adolescent Diabetes. Samples were previously genotyped for 183, 546 single nucleotide polymorphisms (SNPs) on the Immunochip. HILIC-UPLC was applied for quantification of the N-glycans of both total plasma proteins and IgG. Genome-wide association study identified five genome-wide significant loci associated with total plasma proteins and/or IgG N-glycans. All of the identified loci, except for the complement C3 gene (C3) locus, were previously associated with N-glycosylation. SNPs within the exon regions of the C3 gene are associated with the oligomannose N-glycan levels. C3 protein glycosylation changes within the T1D population and their influence on complement activation should be further investigated. In the follow- up experiments, N-glycans from 187 children with T1D and their 244 unaffected siblings were quantified. Our results showed that children with a recent diagnosis of T1D had significantly higher levels of mannose and GlcNAc terminal residues on total plasma proteins and IgG, respectively, when compared to their unaffected siblings. This suggests that the complement system could be activated in T1D through the mannose-binding lectin pathway.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Farmacija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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